POS1544 LONG-TERM SAFETY AND EFFICACY OF TOFACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS BY PRIOR BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUG EXPOSURE
Authors: D. D. Gladman, M. Dougados, H. Marzo-Ortega, M. J. Cadatal, C. Kinch, P. Nash
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Patients (pts) with psoriatic arthritis (PsA) exposed to tumour necrosis factor inhibitors (TNFi) may have attenuated response or higher adverse event (AE) risk with subsequent treatment. Tofacitinib efficacy/safety in PsA pts was shown in 3 Phase (P)3 trials and 1 long-term extension (LTE) trial. <h3>Objectives</h3> Assess long-term safety/efficacy of tofacitinib in TNFi-inadequate responder (IR) and biologic disease-modifying antirheumatic drug (bDMARD)-naïve PsA pts. <h3>Methods</h3> Pooled data from P3 trials (NCT01877668/NCT01882439/NCT03486457) of PsA pts receiving ≥1 tofacitinib dose and 1 LTE trial (NCT01976364) of PsA pts receiving tofacitinib 5 mg BID (dose switching allowed after 1 month) were stratified by TNFi-IR or bDMARD-naïve status at P3 trial baseline (BL). Safety assessed in P3/LTE trials. Efficacy assessed in LTE trial only to Month (M)36 (longitudinal models, data as observed): MDA and HAQ-DI (≥0.35 improvement) response rates and change from BL (Δ) in PASDAS. Data reported as all tofacitinib (pts receiving ≥1 tofacitinib dose) or constant tofacitinib 5 mg BID (pts assigned to tofacitinib 5 mg BID in P3/LTE trials or placebo→tofacitinib 5 mg BID in P3 trials and maintained this dose). <h3>Results</h3> 408 TNFi-IR (incl. 29 TNFi-exposed with unknown IR status) and 562 bDMARD-naïve pts from P3/LTE trials were assessed. Differences in P3 trial BL characteristics in TNFi-IR vs bDMARD-naïve pts included longer disease duration (all tofacitinib, mean: 8.9 vs 5.6 years), higher HAQ-DI scores (mean: 1.2 vs 0.9) and a higher proportion (%) of pts aged ≥65 years (9.6 vs 7.7) and from North America (27.5 vs 8.0). Treatment-emergent AE (TEAE) incidence rates were higher in TNFi-IR vs bDMARD-naïve pts; serious AE (SAE), serious infection (SI) and herpes zoster (HZ; all tofacitinib) incidence rates were numerically higher in TNFi-IR vs bDMARD-naïve pts (confidence intervals [CIs] overlapped; Table 1). Deaths, malignancies excl. non-melanoma skin cancer (NMSC), NMSC, major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) events were observed (Table 1). Tofacitinib response/improvements were sustained to M36 in pts remaining in LTE trial, regardless of prior treatment. At all time points, TNFi-IR vs bDMARD-naïve pts had lower MDA response rates and slightly lower HAQ-DI response rates (Figure 1) and ΔPASDAS (all tofacitinib/constant tofacitinib 5 mg BID: M1 -2.3/-2.5 vs -2.9/-3.0; M6 -2.5/-2.8 vs -3.0/-3.1; M12 -2.7/-2.9 vs -3.0/-3.2; M24 -2.9/-3.1 vs -3.2/-3.4; M36 -3.0/-3.2 vs -3.1/-3.4). <h3>Conclusion</h3> For pts remaining in LTE trial, tofacitinib efficacy was greater in bDMARD-naïve vs TNFi-IR pts; response was maintained over time in both groups. Incidence rates were higher for TEAEs and numerically higher for SAE, SI and HZ (all tofacitinib) in TNFi-IR vs bDMARD-naïve pts. Results consistent with other advanced PsA treatments. Limitations included small event numbers, as observed data and BL characteristic differences. <h3>Acknowledgements</h3> This study was sponsored by Pfizer. Medical writing support, under the direction of the authors, was provided by Justine Juana, BHSc, CMC Connect, a division of IPG Health Medical Communications, and was funded by Pfizer, New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med 2022; 175: 1298-1304). <h3>Disclosure of Interests</h3> Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc and UCB, Maxime Dougados Consultant of: AbbVie, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Helena Marzo-Ortega Consultant of: AbbVie, Biogen, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer Inc, Takeda and UCB, Grant/research support from: Janssen, Novartis and UCB, Mary Jane Cadatal Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cassandra Kinch Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Peter Nash Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis and Pfizer Inc, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis and Pfizer Inc.